Hydrogen-bonding patterns in the cocrystal 2-amino-4,6-dimethyl­pyrimidine–terephthalic acid (2/1)

In the crystal structure of the title compound, 2C₆H₉N₃·C₈H₆O₄, terephthalic acid has a crystallographic inversion centre and the dimethyl­pyrimidine mol­ecule shows approximate non-crystallographic mirror and twofold rotation symmetry. The inversion-related pyrimidine mol­ecules form a base pair [R₂²(8) ring motif] via a pair of N—H...N hydrogen bonds. The carboxyl groups of terephthalic acid link the base pairs via O—H...N and N—H...O hydrogen bonds [R₂²(8) motif] to generate a supra­molecular ribbon.

Key indicators

• Single-crystal X-ray study
• T = 293 K
• Mean [sigma](C-C) = 0.002 Å
• R factor = 0.042
• wR factor = 0.123
• Data-to-parameter ratio = 15.9

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT250_ALERT_2_C Large U3/U1 Ratio for Average U(i,j) Tensor ....       2.14
PLAT790_ALERT_4_C Centre of Gravity not Within Unit Cell: Resd.  #          2
              C6 H9 N3

Alert level G
PLAT199_ALERT_1_G Check the Reported _cell_measurement_temperature        293 K
PLAT200_ALERT_1_G Check the Reported _diffrn_ambient_temperature .        293 K

   0 ALERT level A = In general: serious problem
   0 ALERT level B = Potentially serious problem
   2 ALERT level C = Check and explain
   2 ALERT level G = General alerts; check

   2 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   1 ALERT type 2 Indicator that the structure model may be wrong or deficient
   0 ALERT type 3 Indicator that the structure quality may be low
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S1. Comment

Hydrogen bonding plays an important role in molecular recognition and crystal engineering (Desiraju, 1989). Pyrimidine and aminopyrimidine derivatives are components of nucleic acid. Some pyrimidine derivatives act as antifolate drugs (Hunt et al., 1980; Baker & Santi, 1965). Etter and co workers (Etter & Baures, 1988; Etter & Adsmond,1990) studied the hydrogen bonding motifs, packing patterns and intermolecular interactions of some of the cocrystals structures. The crystal structures of aminopyrimidine derivatives (Schwalbe & Williams, 1982), aminopyrimidine cocrystals (Chinnakali et al., 1999) and aminopyrimidine carboxylates (Hu et al., 2002) have been reported in literature. The crystal structure of trimethoprim terephthalate-terephthalic acid (2/1/1) (Hemamalini et al., 2003) has also been reported from our laboratory. Terephthalic acid self assembles via the R₂²(8) motif and forms interesting supramolecular architectures in the form of tapes and sheets (Du et al., 2005). The adducts of carboxylic acids with 2-aminopyrimidines form the familiar R₂²(8) ring motif (Lynch & Jones, 2004). These interactions are of significance in drug design strategies. In the present study, hydrogen bonding patterns involving 2-amino-4,6-dimethyl pyrimidine-terephthalic acid (2/1), are discussed.

An ORTEPII (Johnson, 1976) view of the title compound is shown in Fig. 1. Terephthalic acid has crystallographic inversion symmetry in the middle of the benzene ring, and the dimethylpyrimidine has approximate non-crystallographic mirror or twofold rotation symmetry (m or 2 along N2, C2, C5). The asymmetric unit contains one 2-amino-4,6-dimethylpyrimidine and half of a molecule of terephthalic acid. The observed bond lengths and bond angles are in agreement with the reported crystal structures of 2-aminopyrimidine (Scheinbeim & Schempp, 1976) and terephthalic acid (Bailey & Brown, 1967). The N1 atom and the 2-amino group (N2—H2B) of the pyrimidine ring form an eight membered ring motif [graph set R₂²(8) (Lynch & Jones, 2004)] with the acid molecule via N—H···O and O—H···N hydrogen bonds (Table. 1). This motif has also been observed in crystal structures of 2-aminopyrimidine-terephthalic acid (Goswami, Mahapatra, Ghosh et al., 1999) and 2-aminopyrimidine-fumaric acid (Goswami, Mahapatra, Nigam et al., 1999). This motif has also been reported from our laboratory in the crystal structures of 2-amino-4,6-dimethylpyrimidine-4-hydroxy benzoic acid (1/1) (Balasubramani et al., 2006), 2-amino-4,6-dimethoxy pyrimidine 4-aminobenzoic acid (1/1) (Thanigaimani et al., 2006) and 2-amino-4,6-dimethyl pyrimidine cinnamic acid (1/2) (Balasubramani et al., 2005). Alternatively, the inversion related pyrimidine molecules form a base pair [R₂²(8) ring motif] via a pair of N—H···N hydrogen bonds involving the 2-amino group (N2—H2A) and the pyrimidine N3 atom. This type of base pairing has been reported in the crystal structures of trimethoprim m-chlorobenzoate dihydrate (Baskar Raj et al., 2003), 2-amino-4,6-dimethylpyrimidinium salicylate (Muthiah et al., 2006) and 2-amino-4,6-dimethylpyrimidinium picrate (Subashini et al., 2006). Two such independent R₂²(8) ring motifs generate the supramolecular ribbons shown in the b,c plane of Fig. 2. Here aminopyrimidine is linked to both the heteromeric and homomeric eight membered R₂²(8) ring motifs. Similar hydrogen bonded patterns are also observed in the crystal structure of 2-aminopyrimidine terephthalic acid (Goswami, Mahapatra, Ghosh et al., 1999) where heteromeric ring motifs are only observed. Further the presented crystal structure is stabilized by stacking interactions between the terephthalic acid molecules (Fig. 3) with centroid-centroid distances of 3.9689 (9) Å, slip angle (the angle between the centroid vector and normal to the plane) of 29.31° and perpendicular separation of 3.461 Å. The observed values are in agreement with the aromatic stacking interactions (Hunter, 1994).

Related literature

For related literature, see: Baskar Raj et al. (2003); Lynch & Jones (2004); Du et al. (2005); Muthiah et al. (2006); Subashini et al. (2006); Thanigaimani et al. (2006); Bailey & Brown (1967); Baker & Santi (1965); Balasubramani et al. (2005, 2006); Chinnakali et al. (1999); Desiraju (1989); Etter & Adsmond (1990); Etter & Baures (1988); Goswami, Mahapatra, Ghosh, Nigam, Chinnakali & Fun (1999); Goswami, Mahapatra, Nigam, Chinnakali, Fun & Razak (1999); Hemamalini et al. (2003); Hu et al. (2002); Hunt et al. (1980); Hunter (1994); Johnson (1976); Scheinbeim & Schempp (1976); Schwalbe & Williams (1982).

S2. Experimental

A hot methanol solution of 2-amino-4,6-dimethylpyrimidine (30 mg, Aldrich) and terephthalic acid (41 mg, Merck) were mixed in 1:1 molar ratio and warmed in a water bath for 30 minutes. On slow evaporation, plate-like crystals of compound the title compound were obtained.

S3. Refinement

All the hydrogen atoms were positioned geometrically and constrained to ride on their parent atoms with U_iso(H)= 1.2Ueq(C). The C—H, O—H and N—H distances are 0.93 - 0.96 Å, 0.82 Å and 0.86 Å respectively.

Computing details

Data collection: APEX2 (Bruker, 2004); cell refinement: APEX2/SAINT (Bruker, 2004); data reduction: SAINT/XPREP (Bruker, 2004); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: PLATON (Spek, 2003); software used to prepare material for publication: PLATON (Spek, 2003).

Figures

	Fig. 1. The molecular structure of (I), showing 50% probability displacement ellipsoids. Dashed lines indicate hydrogen bonds. Inversion related atoms are labelled with "a".
	Fig. 2. View of a two-dimensional motif of supramolecular ribbons along the [1 0 0] direction. Hydrogen bonds are indicated by dashed lines. [Symmetry code: -x, -y + 2, -z]
	Fig. 3. View of the crystal packing along the [1 0 1] direction showing the herring bone motif and the stacking of neighbouring ribbons.

2-amino-4,6-dimethylpyrimidine–terephthalic acid (2/1)

Crystal data

2C6H9N3·C8H6O4	F(000) = 436
Mr = 412.45	Dx = 1.375 Mg m^−3
Monoclinic, P21/n	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2yn	Cell parameters from 3678 reflections
a = 3.9689 (2) Å	θ = 1.8–27.2°
b = 15.1778 (8) Å	µ = 0.10 mm^−1
c = 16.5995 (8) Å	T = 293 K
β = 95.083 (3)°	Plate-like, colourless
V = 996.01 (9) Å^3	0.22 × 0.20 × 0.16 mm
Z = 2

Data collection

Bruker Kappa APEXII diffractometer	1685 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.030
Graphite monochromator	θmax = 27.2°, θmin = 1.8°
ω and ϕ scan	h = −5→5
Absorption correction: multi-scan (SADABS; Bruker, 2004; Blessing, 1995)	k = −19→19
Tmin = 0.969, Tmax = 0.978	l = −21→21
10926 measured reflections	1 standard reflections every 100 reflections
2198 independent reflections

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.042	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.123	H-atom parameters constrained
S = 1.08	w = 1/[σ^2(Fo^2) + (0.0635P)^2 + 0.2062P] where P = (Fo^2 + 2Fc^2)/3
2198 reflections	(Δ/σ)max < 0.001
138 parameters	Δρmax = 0.24 e Å^−3
0 restraints	Δρmin = −0.18 e Å^−3

Special details

Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All e.s.d.'s are estimated from the variances of the (full) variance-covariance matrix. The cell e.s.d.'s are taken into account in the estimation of distances, angles and torsion angles

Refinement. Refinement on F² for ALL reflections except those flagged by the user for potential systematic errors. Weighted R-factors wR and all goodnesses of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The observed criterion of F² > σ(F²) is used only for calculating -R-factor-obs etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
O1	0.0917 (3)	0.60043 (7)	0.31830 (6)	0.0423 (4)
O2	0.3105 (3)	0.47269 (8)	0.28173 (6)	0.0494 (4)
C9	0.2581 (4)	0.52744 (10)	0.33266 (8)	0.0315 (5)
C10	0.3850 (4)	0.51463 (9)	0.41970 (8)	0.0279 (4)
C11	0.3215 (4)	0.57593 (10)	0.47848 (8)	0.0331 (5)
C12	0.4362 (4)	0.56113 (10)	0.55841 (8)	0.0327 (5)
N1	−0.1629 (3)	0.63231 (8)	0.16925 (6)	0.0277 (3)
N2	0.0773 (4)	0.51007 (8)	0.11590 (7)	0.0385 (4)
N3	−0.2311 (3)	0.60097 (8)	0.02749 (6)	0.0298 (4)
C2	−0.1084 (4)	0.58227 (9)	0.10406 (8)	0.0279 (4)
C4	−0.4185 (4)	0.67319 (9)	0.01642 (8)	0.0291 (4)
C5	−0.4849 (4)	0.72782 (10)	0.07997 (8)	0.0310 (4)
C6	−0.3484 (4)	0.70539 (9)	0.15686 (8)	0.0281 (4)
C7	−0.5565 (4)	0.69249 (11)	−0.06899 (9)	0.0392 (5)
C8	−0.3990 (4)	0.76140 (11)	0.22893 (9)	0.0384 (5)
H1	0.02920	0.60360	0.27000	0.0630*
H11	0.20170	0.62700	0.46410	0.0400*
H12	0.39290	0.60230	0.59770	0.0390*
H2A	0.11570	0.47710	0.07560	0.0460*
H2B	0.15940	0.49620	0.16390	0.0460*
H5	−0.61720	0.77810	0.07120	0.0370*
H7A	−0.37370	0.70710	−0.10080	0.0590*
H7B	−0.71100	0.74120	−0.06920	0.0590*
H7C	−0.67290	0.64150	−0.09150	0.0590*
H8A	−0.46280	0.72480	0.27220	0.0580*
H8B	−0.57440	0.80370	0.21500	0.0580*
H8C	−0.19220	0.79160	0.24580	0.0580*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0618 (8)	0.0386 (6)	0.0242 (5)	0.0146 (6)	−0.0083 (5)	0.0019 (4)
O2	0.0752 (9)	0.0448 (7)	0.0261 (5)	0.0172 (6)	−0.0075 (5)	−0.0038 (5)
C9	0.0373 (9)	0.0316 (8)	0.0252 (7)	−0.0003 (7)	−0.0002 (6)	0.0023 (6)
C10	0.0309 (8)	0.0277 (7)	0.0247 (6)	−0.0018 (6)	−0.0001 (5)	0.0021 (5)
C11	0.0399 (9)	0.0290 (8)	0.0297 (7)	0.0075 (7)	−0.0016 (6)	0.0025 (6)
C12	0.0416 (9)	0.0303 (8)	0.0258 (7)	0.0040 (7)	0.0015 (6)	−0.0023 (5)
N1	0.0332 (7)	0.0285 (6)	0.0209 (5)	−0.0012 (5)	−0.0004 (4)	−0.0006 (4)
N2	0.0585 (9)	0.0350 (7)	0.0208 (6)	0.0117 (6)	−0.0026 (5)	−0.0023 (5)
N3	0.0369 (7)	0.0314 (7)	0.0205 (5)	−0.0041 (5)	−0.0009 (5)	0.0004 (5)
C2	0.0339 (8)	0.0283 (7)	0.0213 (6)	−0.0052 (6)	0.0007 (5)	−0.0001 (5)
C4	0.0290 (8)	0.0323 (8)	0.0250 (7)	−0.0074 (6)	−0.0025 (5)	0.0040 (5)
C5	0.0333 (8)	0.0293 (8)	0.0299 (7)	−0.0002 (6)	−0.0008 (6)	0.0034 (6)
C6	0.0290 (8)	0.0291 (7)	0.0259 (7)	−0.0041 (6)	0.0010 (5)	0.0003 (5)
C7	0.0444 (10)	0.0436 (9)	0.0277 (7)	−0.0029 (7)	−0.0073 (6)	0.0056 (6)
C8	0.0445 (10)	0.0391 (9)	0.0314 (7)	0.0039 (7)	0.0019 (6)	−0.0047 (6)

Geometric parameters (Å, º)

O1—C9	1.3009 (19)	C11—H11	0.9294
O2—C9	1.2164 (18)	C12—H12	0.9302
O1—H1	0.8194	C4—C5	1.385 (2)
N1—C2	1.3550 (17)	C4—C7	1.503 (2)
N1—C6	1.3371 (19)	C5—C6	1.3842 (19)
N2—C2	1.326 (2)	C6—C8	1.496 (2)
N3—C2	1.3504 (17)	C5—H5	0.9305
N3—C4	1.3283 (19)	C7—H7A	0.9603
N2—H2B	0.8598	C7—H7B	0.9603
N2—H2A	0.8598	C7—H7C	0.9599
C9—C10	1.5000 (19)	C8—H8A	0.9596
C10—C12^i	1.383 (2)	C8—H8B	0.9601
C10—C11	1.387 (2)	C8—H8C	0.9599
C11—C12	1.3824 (19)
C9—O1—H1	109.51	C5—C4—C7	121.58 (13)
C2—N1—C6	117.83 (11)	N3—C4—C5	122.04 (12)
C2—N3—C4	117.03 (11)	N3—C4—C7	116.37 (12)
H2A—N2—H2B	119.98	C4—C5—C6	118.01 (14)
C2—N2—H2B	119.99	N1—C6—C5	120.73 (12)
C2—N2—H2A	120.02	N1—C6—C8	117.36 (12)
O2—C9—C10	121.16 (14)	C5—C6—C8	121.90 (13)
O1—C9—O2	124.73 (13)	C4—C5—H5	120.97
O1—C9—C10	114.11 (12)	C6—C5—H5	121.02
C11—C10—C12^i	119.59 (13)	C4—C7—H7A	109.50
C9—C10—C11	121.61 (13)	C4—C7—H7B	109.43
C9—C10—C12^i	118.79 (12)	C4—C7—H7C	109.43
C10—C11—C12	120.08 (14)	H7A—C7—H7B	109.48
C10^i—C12—C11	120.33 (13)	H7A—C7—H7C	109.46
C10—C11—H11	119.96	H7B—C7—H7C	109.52
C12—C11—H11	119.97	C6—C8—H8A	109.43
C11—C12—H12	119.88	C6—C8—H8B	109.47
C10^i—C12—H12	119.79	C6—C8—H8C	109.44
N1—C2—N2	118.10 (12)	H8A—C8—H8B	109.49
N1—C2—N3	124.34 (13)	H8A—C8—H8C	109.49
N2—C2—N3	117.56 (12)	H8B—C8—H8C	109.51
C6—N1—C2—N3	−0.5 (2)	O1—C9—C10—C12^i	179.68 (14)
C2—N1—C6—C8	−178.37 (13)	C12^i—C10—C11—C12	−0.1 (2)
C6—N1—C2—N2	179.54 (14)	C9—C10—C12^i—C11^i	−178.67 (14)
C2—N1—C6—C5	1.2 (2)	C9—C10—C11—C12	178.64 (14)
C4—N3—C2—N1	−0.3 (2)	C11—C10—C12^i—C11^i	0.1 (2)
C4—N3—C2—N2	179.61 (14)	C10—C11—C12—C10^i	0.1 (2)
C2—N3—C4—C7	−179.30 (13)	C7—C4—C5—C6	179.98 (14)
C2—N3—C4—C5	0.5 (2)	N3—C4—C5—C6	0.2 (2)
O1—C9—C10—C11	0.9 (2)	C4—C5—C6—N1	−1.1 (2)
O2—C9—C10—C11	−178.85 (15)	C4—C5—C6—C8	178.48 (14)
O2—C9—C10—C12^i	−0.1 (2)

Symmetry code: (i) −x+1, −y+1, −z+1.

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1···N1	0.82	1.83	2.6332 (14)	167
N2—H2A···N3^ii	0.86	2.16	3.0225 (16)	177
N2—H2B···O2	0.86	2.03	2.8817 (16)	173

Symmetry code: (ii) −x, −y+1, −z.